A 2-Week Ketogenic Diet in Combination With Letrozole to Modulate PI3K Signaling in ER+ Breast Cancer

NCT ID: NCT03962647

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-08
• Study Completion Date: 2024-07-14

Brief Summary

This is a neoadjuvant study to determine the feasibility and tolerability of 2 weeks of a very low carbohydrate ketogenic diet in combination with letrozole for patients with early stage operable ER+disease.

Detailed Description

Primary Objective:

• To evaluate the feasibility and tolerability of a 2 week ketogenic diet in combination with endocrine therapy prior to surgery for early stage ER+ breast cancer.

Secondary Objectives

• To determine whether endocrine therapy in combination with a dietary intervention to reduce insulin pathway signaling results in enhanced inhibition of cancer cell proliferation (measured byKi67)
• To determine the effectiveness of 2 weeks of a ketogenic diet to reduce measures of insulin/PI3Kpathway activation in breast tumors
• To measure changes in weight and body composition after 2 weeks of a ketogenic diet
• To measure changes in insulin resistance after 2 weeks of a ketogenic diet
• To measure the effectiveness of a ketogenic diet in combination with endocrine therapy to induce and maintain a ketogenic state.

Outline:

Participants will have baseline metabolic parameters measured and will begin a 2-week diet consisting of meal replacement shakes to induce a ketogenic state. Patients will also receive letrozole 2.5 mg daily. At the end of 2 weeks, metabolic parameters will again be measured and patients will proceed with surgical treatment of their breast cancer. A tumor biopsy from the surgical specimen will be obtained to measure cell proliferation compared with the pre-treatment diagnostic biopsy.

Conditions

Estrogen Receptor-positive Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

2-Week Ketogenic Diet

2-Week Ketogenic Diet in Combination with Letrozole

Group Type: EXPERIMENTAL

2-Week Ketogenic Diet

Intervention Type: DIETARY_SUPPLEMENT

2-Week Ketogenic Diet in Combination with Letrozole

Letrozole

Intervention Type: DRUG

2.5 mg taken once daily by mouth

Letrozole Control

Group Type: ACTIVE_COMPARATOR

Letrozole

Intervention Type: DRUG

2.5 mg taken once daily by mouth

Interventions

2-Week Ketogenic Diet

2-Week Ketogenic Diet in Combination with Letrozole

Intervention Type: DIETARY_SUPPLEMENT

Letrozole

2.5 mg taken once daily by mouth

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• All participants must provide written informed consent.
• Patients must have histologically confirmed primary invasive mammary carcinoma

• The tumor must be estrogen receptor positive
• The tumor must be HER2 negative (negative IHC or FISH)
• The primary tumor size must be at least 2 mm in size.
• Patients must be post-menopausal defined by any of the following:

• Subjects at least 55 years of age.
• Subjects younger than 55 years of age and amenorrheic for at least 12 months or serum follicle-stimulating hormone (FSH) levels and estradiol levels in the post-menopausal range by local lab criteria
• Subjects with history of bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months.
• Patients must have clinical stage I, II, or III invasive mammary carcinoma planning to undergo surgical treatment with either segmental resection or total mastectomy.
• Patients must have BMI >= 30.
• A core biopsy from the time of diagnosis must be available.
• Mammogram or ultrasound required prior to screening
• Patients must have adequate organ function based on the following laboratory parameters:

• Serum creatinine <= 1.5x ULN
• SGOT, SGPT <= 4x ULN (unless known steatohepatitis)
• Serum albumin >= 2.0 g/dL
• Total serum bilirubin <= 1.5x ULN (or <= 3x ULN if known Gilbert's syndrome)

Exclusion Criteria

Patients with locally advanced disease who are candidates for other preoperative (chemo)therapy at the time of initial evaluation. This includes patients with inflammatory breast cancer.

• Evidence of distant metastatic disease (stage IV).
• Serious medical illness that in the judgment of the treating physician places the patient at high risk of operative mortality.
• Serious medical illness that in the judgment of the treating physician would preclude the use of a ketogenic diet.
• Severe uncontrolled malabsorption condition or disease (e.g. grade II/III diarrhea, severe malnutrition, short gut syndrome).
• Diabetes mellitus requiring insulin therapy.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Participation in any other neoadjuvant therapeutic clinical trial.
• Concurrent anti-cancer therapy other than endocrine therapy (e.g. chemotherapy, radiotherapy, immunotherapy, or any other biologic therapy).
• Concurrent treatment with an investigational agent.
• Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first day of dietary intervention.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Brent Rexer

Sponsor Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brent Rexer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt Medical Center

Locations

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

VICC BRE 18108

Identifier Type: -

Identifier Source: org_study_id

NCI-2019-03071

Identifier Type: REGISTRY

Identifier Source: secondary_id